A review of the underlying genetics and emerging therapies for canine cardiomyopathies

Cardiomyopathies such as dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are common in large breed dogs and carry an overall poor prognosis. Research shows that these diseases have strong breed predilections, and selective breeding has historically been recommended to redu...

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Bibliographic Details
Published in:	Journal of veterinary cardiology Vol. 40; pp. 2 - 14
Main Authors:	Shen, L., Estrada, A.H., Meurs, K.M., Sleeper, M., Vulpe, C., Martyniuk, C.J., Pacak, C.A.
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 01-04-2022
Subjects:	Animals Arrhythmogenic right ventricular cardiomyopathy Arrhythmogenic Right Ventricular Dysplasia - veterinary Cardiomyopathies - genetics Cardiomyopathies - therapy Cardiomyopathies - veterinary Cardiomyopathy, Dilated - genetics Cardiomyopathy, Dilated - therapy Cardiomyopathy, Dilated - veterinary Clustered regularly interspaced short palindromic repeats Dilated cardiomyopathy Dog Diseases - genetics Dog Diseases - therapy Dogs Gene editing Gene therapy Heart Failure - veterinary Mutation Clustered regularly interspaced short palindromic repeats Dilated cardiomyopathy Arrhythmogenic right ventricular cardiomyopathy Gene therapy Gene editing
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Summary:	Cardiomyopathies such as dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are common in large breed dogs and carry an overall poor prognosis. Research shows that these diseases have strong breed predilections, and selective breeding has historically been recommended to reduce the disease prevalence in affected breeds. Treatment of these diseases is typically palliative and aimed at slowing disease progression and managing clinical signs of heart failure as they develop. The discovery of specific genetic mutations underlying cardiomyopathies, such as the striatin mutation in Boxer arrhythmogenic right ventricular cardiomyopathy and the pyruvate dehydrogenase kinase 4 and titin mutations in Doberman Pinschers, has strengthened our ability to screen and selectively breed individuals in an attempt to produce unaffected offspring. The discovery of these disease-linked mutations has also opened avenues for the development of gene therapies, including gene transfer and genome-editing approaches. This review article discusses the known genetics of cardiomyopathies in dogs, reviews existing gene therapy strategies and the status of their development in canines, and discusses ongoing challenges in the clinical translation of these technologies for treating heart disease. While challenges remain in using these emerging technologies, the exponential growth of the gene therapy field holds great promise for future clinical applications.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1
ISSN:	1760-2734 1875-0834
DOI:	10.1016/j.jvc.2021.05.003